Agitation and Irritability in Alzheimer’s Disease: Evidenced-Based Treatments and the Black-Box Warning
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More than five million Americans suffer from Alzheimer’s disease (AD), and this number is expected to triple by 2050. While impairments in cognition, particularly memory, are typically the defining features of the clinical syndrome, behavioral symptoms are extremely common, affecting up to 90 % of patients. Behavioral symptoms in AD can be difficult to manage and may require a combination of non-pharmacological and pharmacological approaches. The latter is complicated by FDA “black-box warnings” for the medication classes most often used to target these symptoms, and currently there are initiatives in place to limit their use. In this review, we describe common behavioral symptoms of AD—with a particular focus on the challenging symptoms of “agitation” and “irritability”—and discuss evidence-based approaches to their management. Ultimately, multidimensional approaches must be tailored to the patient and their environment, though evidence-based practices should define the treatment of agitation and irritability in AD.
KeywordsAlzheimer’s disease Neuropsychiatric symptoms Pharmacological approaches Non-pharmacological approaches Black-box warning
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Conflict of Interest
The authors declare that they have no competing interests.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
This work was supported, in part, by National Institutes of Health grant T32 MH1711929 (AMK).
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- 11.Charernboon T, Phanasathit M. Prevalence of neuropsychiatric symptoms in Alzheimer’s disease: a cross-sectional descriptive study in Thailand. J Med Assoc Thail. 2014;97:560–5.Google Scholar
- 12.Thyrian JR, Eichler T, Hertel J, Wucherer D, Dreier A, Michalowsky B, Killimann I, Teipel S, Hoffmann W. Burden of behavioral and psychiatric symptoms in people screened positive for dementia in primary care: results of the DelpHi-study. J Alzheimers Dis. 2015.Google Scholar
- 13.••Kales HC, Gitlin LN, Lyketsos CG, Detroit Expert Panel on A, Management of Neuropsychiatric Symptoms of D. Management of neuropsychiatric symptoms of dementia in clinical settings: recommendations from a multidisciplinary expert panel. J Am Geriatr Soc. 2014;62:762–9. Recommendations from expert panel, with excellent review of the DICE approach.PubMedCentralCrossRefPubMedGoogle Scholar
- 14.Conde-Sala JL, Turro-Garriga O, Pinan-Hernandez S, Portellano-Ortiz C, Vinas-Diez V, Gascon-Bayarri J, Rene-Ramirez R. Effects of anosognosia and neuropsychiatric symptoms on the quality of life of patients with Alzheimer’s disease: a 24-month follow-up study. Int J Geriatr Psychiatry. 2015.Google Scholar
- 17.•Peters ME, Schwartz S, Han D, Rabins PV, Steinberg M, Tschanz JT, et al. Neuropsychiatric symptoms as predictors of progression to severe Alzheimer’s dementia and death: the Cache County Dementia Progression Study. Am J Psychiatry. 2015;172:460–5. Recently published analysis of data from the Cache County Dementia Progression Study, examining the relationship between neuropsychiatric symptoms and progression to severe dementia or death.CrossRefPubMedGoogle Scholar
- 20.Soto M, Andrieu S, Nourhashemi F, Ousset PJ, Ballard C, Robert P, Vellas B, Lyketsos CG, Rosenberg PB Medication development for agitation and aggression in Alzheimer disease: review and discussion of recent randomized clinical trial design. Int Psychogeriatr. 2014;1–17.Google Scholar
- 21.Stella F, Forlenza OV, Laks J, de Andrade LP, de Castilho Cacao J, Govone JS, de Medeiros K, Lyketsos CG. Caregiver report versus clinician impression: disagreements in rating neuropsychiatric symptoms in Alzheimer’s disease patients. Int J Geriatr Psychiatry. 2015.Google Scholar
- 29.Karel MJ, Teri L, McConnell E, Visnic S, Karlin BE. Effectiveness of expanded implementation of STAR-VA for managing dementia-related behaviors among veterans. Gerontologist. 2015.Google Scholar
- 31.Figueiro MG, Plitnick BA, Lok A, Jones GE, Higgins P, Hornick TR, et al. Tailored lighting intervention improves measures of sleep, depression, and agitation in persons with Alzheimer’s disease and related dementia living in long-term care facilities. Clin Interv Aging. 2014;9:1527–37.PubMedCentralCrossRefPubMedGoogle Scholar
- 38.FDA U. U.S. Government. 2008.Google Scholar
- 40.Singh RR, Nayak R. Impact of FDA black box warning on psychotropic drug use in noninstitutionalized elderly patients diagnosed with dementia: a retrospective study. J Pharm Pract. 2015.Google Scholar
- 41.•Maust DT, Kim HM, Seyfried LS, Chiang C, Kavanagh J, Schneider LS, et al. Antipsychotics, other psychotropics, and the risk of death in patients with dementia: number needed to harm. JAMA Psychiatry. 2015;72:438–45. Recent retrospective case–control study suggesting that the effect of antipsychotics on mortality in elderly patients with dementia may be higher than previously reported.CrossRefPubMedGoogle Scholar
- 43.M M, AR M, J H, Z W, R S, PG S, B R, L H, MJ S, BA E, A M, T. P. Agency for Healthcare Research and Quality (US), Rockville, MD. 2011.Google Scholar
- 50.••Berryman SN, Jennings J, Ragsdale S, Lofton T, Huff DC, Rooker JS. Beers criteria for potentially inappropriate medication use in older adults. Medsurg Nurs. 2012;21:129–32. Quiz 133. Important update to Beers Criteria from the American Geriatrics Society, highlighting medications that should be prescribed with caution in the older adult population.PubMedGoogle Scholar
- 53.•Porsteinsson AP, Drye LT, Pollock BG, Devanand DP, Frangakis C, Ismail Z, et al. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA. 2014;311:682–91. Results from the CiTAD clinical trial, showing that citalopram significantly reduced agitation in individuals with Alzheimer’s disease (as compared to placebo).PubMedCentralCrossRefPubMedGoogle Scholar
- 56.Ballard C, Thomas A, Gerry S, Yu LM, Aarsland D, Merritt C, et al. A double-blind randomized placebo-controlled withdrawal trial comparing memantine and antipsychotics for the long-term treatment of function and neuropsychiatric symptoms in people with Alzheimer’s disease (MAIN-AD). J Am Med Dir Assoc. 2015;16:316–22.CrossRefPubMedGoogle Scholar
- 57.Voyer P, McCusker J, Cole MG, Monette J, Champoux N, Ciampi A, et al. Behavioral and psychological symptoms of dementia: how long does every behavior last, and are particular behaviors associated with PRN antipsychotic agent use? J Gerontol Nurs. 2015;41:22–37. quiz 38–29.CrossRefPubMedGoogle Scholar
- 59.Martin D, MacVicar S. Drugging dementia: are antipsychotics killing nursing home patients? Aljazeera America. 2015.Google Scholar
- 60.CMS. Center for Medicare & Medcaid Services, CMS.gov. 2014.Google Scholar
- 64.•Brendel RW, Wei MH, Schouten R, Edersheim JG. An approach to selected legal issues: confidentiality, mandatory reporting, abuse and neglect, informed consent, capacity decisions, boundary issues, and malpractice claims. Med Clin N Am. 2010;94:1229–40. xi-ii. Review of approaches to common medicolegal issues, including capacity decisions and informed consent.CrossRefPubMedGoogle Scholar